title: Efficacy of adenovirally expressed soluble TRAIL in human glioma organotypic slice culture and glioma xenografts.
abstract: Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in malignant cells, including gliomas, and is currently in anticancer clinical trials. However, the full-length and tagged forms of TRAIL, unlike the untagged ligand (soluble TRAIL (sTRAIL)), exhibits toxicity against normal cells. Here, we report the generation and testing of an adenovirus (AdsTRAIL) that expresses untagged sTRAIL in an intracranial xenograft model and a human glioma organotypic slice culture model. AdsTRAIL efficiently induced apoptosis in glioma cell lines, including those resistant to sTRAIL, but not in normal human astrocytes (NHAs). It inhibited anchorage-independent glioma growth and exerted a bystander effect in transwell assays. Intratumoral injections of AdsTRAIL in a rodent intracranial glioma model resulted in reduced tumor growth and improved survival compared with Ad-enhanced green fluorescent protein (EGFP)- or vehicle-treated controls without toxicity. Human glioma organotypic slices treated with AdsTRAIL demonstrated apoptosis induction and caspase activation.
authors.affiliation: Department of Neuro-oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77035, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: X
authors.initials: X
authors.lastname: Xie
authors.forename: S
authors.initials: S
authors.lastname: Prabhu
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.forename: D
authors.initials: D
authors.lastname: Sampath
authors.forename: K
authors.initials: K
authors.lastname: Aldape
authors.forename: G
authors.initials: G
authors.lastname: Fuller
authors.forename: V K
authors.initials: VK
authors.lastname: Puduvalli
mesh_terms: D000256:Adenoviridae / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D005629:Frozen Sections; D015316:Genetic Therapy / Q000295:instrumentation; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D005910:Glioma / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand